ABSTRACT Percutaneous Nephrolithotomy (PCNL) suffers from lack of sufficient dexterity of the nephroscope to access stag horn and complex stones through a single insertion port, therefore necessitating multiple procedures or creation of several access tracts to treat the entire stone. Multiple procedures or access tracts can increase parenchyma damage, blood loss, complication rates and healthcare costs. Therefore, there is a need for improving the current method of performing PCNL by enhancing access of the nephroscope to large and complex stones in the pelvicalyceal anatomy through an optimal port. Our long-term goal is to develop a robotic endoscope that can access the entire stone through a single insertion port with accurate guidance to minimize complications. The objective of this grant is to improve access to the stone by designing and developing an image-registered hand-held concentric tube robot (CTR) instrumented with a position sensor, mini fiberscope and laser ablation fiber. In order to minimize the number of tracts created, we will also develop an optimization algorithm for calculating the ?optimal? puncture location and desired trajectory for the CTR. The rationale that underlies the proposed research is that the CTR inserted along a desired trajectory through an optimal port will enable the urologist to safely obtain access to the entire stone through a single tract, thereby ensuring complete stone removal while minimizing damage to the kidney parenchyma. In addition, the navigation system will aid in visualizing and targeting the stones in 3 dimensions, thereby providing enhanced depth perception compared to the standard 2D projection fluoroscopy. We plan to achieve the objective by pursuing the following specific aims: 1) Develop a hand-held CTR device instrumented with a position sensor to cover the entire calyx and deliver the laser fiber. We will also develop an algorithm to evaluate the optimal puncture location to enable access to the entire stone while maximizing the dexterity of the CTR. 2) Develop surgical navigation software that fuses the diagnostic CT and intraoperative tracked ultrasound images to visualize the CTR and neighboring anatomy in real-time. 3) Validate the CTR device and navigation system in ex-vivo kidney tissue and porcine models. The proposed research is significant since it will enable a higher stone-free rate while reducing the complication rate associated with the PCNL procedure. The proposed research is innovative in that it builds on state-of-the-art CTR technology, motion planning and navigation algorithms, and mixed-reality visualization modalities to enable urologists to accurately and safely target kidney calculi during PCNL.